用于增强肺癌早期检测的无细胞 DNA 片段组测定的临床验证。

IF 29.7 1区 医学 Q1 ONCOLOGY Cancer discovery Pub Date : 2024-11-01 DOI:10.1158/2159-8290.CD-24-0519
Peter J Mazzone, Peter B Bach, Jacob Carey, Caitlin A Schonewolf, Katalin Bognar, Manmeet S Ahluwalia, Marcia Cruz-Correa, David Gierada, Sonali Kotagiri, Kathryn Lloyd, Fabien Maldonado, Jesse D Ortendahl, Lecia V Sequist, Gerard A Silvestri, Nichole Tanner, Jeffrey C Thompson, Anil Vachani, Kwok-Kin Wong, Ali H Zaidi, Joseph Catallini, Ariel Gershman, Keith Lumbard, Laurel K Millberg, Jeff Nawrocki, Carter Portwood, Aakanksha Rangnekar, Carolina Campos Sheridan, Niti Trivedi, Tony Wu, Yuhua Zong, Lindsey Cotton, Allison Ryan, Christopher Cisar, Alessandro Leal, Nicholas Dracopoli, Robert B Scharpf, Victor E Velculescu, Luke R G Pike
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引用次数: 0

摘要

每年通过低剂量计算机断层扫描(LDCT)进行肺癌筛查的采用率很低。我们在 958 名符合肺癌筛查条件的人中开展了一项前瞻性病例对照研究,以开发一种基于血液的肺癌检测试验,当检测结果呈阳性时再进行 LDCT 检查。外周血中全基因组无细胞DNA(cfDNA)片段图谱(片段组)的变化反映了肺癌的基因组和染色质特征。我们将机器学习应用于片段组特征,以确定哪些人患肺癌的可能性更大,哪些人患肺癌的可能性更小。我们使用研究样本中的 576 例病例和对照组对分类器进行了训练,然后在 382 例病例和对照组中进行了验证。验证结果表明,分类器对肺癌的灵敏度很高,而且在不同人口群体和合并症方面具有一致性。在一个五年期模型中,将测试结果应用于符合筛查条件的人群,并假定使用率不高,这表明该模型有可能预防数千例肺癌死亡。
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Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection.

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025.

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来源期刊
Cancer discovery
Cancer discovery ONCOLOGY-
CiteScore
22.90
自引率
1.40%
发文量
838
审稿时长
6-12 weeks
期刊介绍: Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.
期刊最新文献
Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection. The N6-methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma. Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma. A Classical Epithelial State Drives Acute Resistance to KRAS Inhibition in Pancreatic Cancer. Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer.
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